The present invention relates to an antimicrobial lipid-containing oil-in-water emulsion which inactivatcs infectious pathogens upon contact.
Oil-in-water emulsions have discrete droplets of oil, called the "discominuous phase," dispersed in a "continuous phase" of water or an aqueous solvent. The discontinuous phase of the emulsion of the present invention binds to the biological membrane of a pathogen and subsequently solubilizes the membrane. The emulsion has microbicidal activity against a broad spectrum of bacteria and several yeasts.
It is known that if a water-iminiscible liquid phase, is mixed imo an aqueous phase by mechanical agitation, for example, by means of an ultra-disperser, the stability of the resulting oil-in-water dispersion most frequently requires the addition of an emulsifying agent, the molecules of which are adsorbed onto the surface of the oil droplets to form a kind of continuous membrane which prevents direct contact between two adjacent droplets. The drops of oil can further contain substances soluble in an organic medium, such as a sterol.
In addition to discrete oil droplets dispersed in an aqueous phase, oil-in-water emulsions can also contain other lipid structures, such as small lipid vesicles (i.e., lipid spheres which often consist of several substantially concentric lipid bilayers separated from each other by layers of aqueous phase), micelles (i.e., amphiphile molecules in small clusters of 50-200 molecules arranged so that the polar head groups face outward toward the aqueous phase and the apolar tails are sequestered inward away from the aqueous phase), or lamellar phases (lipid dispersions in which each particle consists of parallel amphiphile bilayers separated by thin films of water). TheSe lipid structures are formed as a result ofhydrophobic forces which drive apolar residues (i.e., long hydrocarbon chains) away from water.
The antimicrobial emulsion of the presem invemion consists primarily of positively charged droplets of a lipid-comaining oily discominuous phase dispersed in an aqueous cominuous phase, such as water. The discominuous phase comains an amphiphile selected from the group consisting of glycerol monooleate, glycerol trioleate, glycerol monolaurate, and glycerol dilaurate as the primary lipid and a cationic halogen-containing compound having a C.sub.12 -C.sub.16 chain as a positive charge producing agent. The droplets can further contain a sterol, such as cholesterol or phytosterol. The droplets bind to negatively charged proteins contained in bacterial, viral, or fungal membranes, thereby disrupting the membrane structure and irradiating the pathogen.
Antimicrobial emulsions of the present invention are non-toxic and safe, for example, when swallowed, inhaled, or applied to the skin. This result is unexpected since many cationic halogen-containing compounds having a C.sub.12 -C.sub.16 chain are extremely toxic if administered alone. For example, cetylpyridinium chloride (CPC), a preferred cationic halogen-containing compound of the invention, causes severe irritation and damage to tissues of the upper respiratory tract, mucous membranes and skin. However, when administered in the form of an emulsion of the invention, no such adverse effects occur. Furthermore, the emulsions of the invention are stable when heated or exposed to significant levels of acid and base.
The portals of entry of pathogenic bacteria, viruses or fungi are predominantly the skin and mucus membranes. The first step in any infection is attachment or colonization on skin or mucus membranes with subsequent invasion and dissemination of the infectious pathogen. Accordingly, an object of the present invention is to provide an antimicrobial emulsion which inactivates infectious pathogens on contact by disrupting their membrane structures.